Method for improving the in-vivo strength of polyglycolic acid

ABSTRACT

POLYGLYCOLIC ACID IN SHAPED FORM (I.E. A SUTURE) WHICH IS SUBSTANTIALLY FREE FROM VAPORIZABLE IMPURITIES IS PROVIDED WHICH HAS SIGNIFICANTLY GREATER IN-VIVO STRENGTH RETENTION THAN SHAPED POLYGLYCOLIC ACID CONTAINING SAID VAPORIZABLE IMPURITIES. THE IMPORVED POLYGLYCOLIC ACID IS PREPARED BY VACUUM HEATING SHAPED POLYGLYCOLIC ACID CONTAINING VAPORIZABLE IMPURITIES TO VAPORIZE THE IMPURITIES THEREFROM, AND THEN REMOVING THE VAPORIZED IMPURITIES FROM THE POLYGLYCOLIC ACID. AN APPARATUS FOR CONVENIENTLY CARRYING OUT THE ABOVE PROCESS IS ALSO PROVIDED.

Nov. 13, 1973' A. GLICK EI'AL 3,772.420

METHOD FOR IMPROVING THE IN-VIVO STRENGTH F POLYGLYCOLIC ACID OriginalFiled Dec. 25, 1968 7 Sheets-Sheet 1- /00 EFFECT 0P TEMPERATURE(PRESSURE: 4 mm. Hg TIME. 5 HOURS) 90 PACKAGE STRAIGHT PULL 0 Q a a0 1 Ig /.5 Q o 70 q E g 3 60 PAC/(AGE K/VOT PULL g 1 a 50 0 S E k 3 40 figWEIGHT Loss Li L. k V) 30 ru w /5 0Ar//v-v/v0 STRAIGHT a l 1 k 0 /00200. r. TEMPERATURE (6) EFFECT OF PRESSURE Q (TEMPERATURE: /35cT/ME-5/10U/P5) Q a 9 .9

S a E 8 .8 E m 3 7 I50AY/AH/l v0 .STRA/GHT PULL 7 3 k a \1 E 6 I V .6 ga CONTROL 1 Q u 5 P 5 u E 0) 4 4 \WEIGHT L055 F 0 E E 0 1 l r l 0ABSOLUTE PPL-ssUPE (mm/1 Nov. 13, 1973 LI ET AL 3,772,420 METHOD FORIMPROVING THE IN-VIVO STRENGTH OF POLYGLYCOLIC ACID Original Filed Dec.23, 1968 7 Sheets-Shoot 2 EFFECT 0F HEAT/N6 TIME (PRESSURE 4mm. Hg)

HEAT/N6 nut/ma) Nov. 13, 1973 RENGTH OF POLYGLYCOLIC ACID 7 Sheets-Shoot3 SIZE /0 SUTURE (AVERAGE VALUES) -'---$/ZE 2-0 .SUTURE (AVERAGE VALUES)Original Filed Dec. 23, 1968 DAYS IMP/.AA/TED //V RABBIT lN-V/l/OTENS/LE STRENGTH (PS/ //V THOUSANDS) Nov. 13, 1973 Original Filed Dec.23, 1968 '7 Sheets-Sheet 4.

TREATED S/ZE 2-0 SUTURE CONTROL 5/25 20 20 sawml I I l l I l l I l 0 0 7DAYS /MPLA/V7'ED //V BABE/7' -fIL-i. 5

Nov. 13, 1973 Original Filed Dec. 23, 1968 A. GLICK ET AL METHOD FORIMPROVING THE IN-VIVO STRENGTH OF POLYGLYCOLIC ACID 7 Sheets-Sheet 53,772,420 ENGTH Nov. 13, 1973 A. GLICK ETAL METHOD FOR IMPROVING THEIN-VIVO STR OF POLYGLYCOLIC ACID 7 Sheets-Sheet 6 Original Filed Dec.23, 1968 FMFTW Nov. 13, 1973 A. GLICK ET AL 3,772,420

METHOD FOR IMPROVING THE IN-VIVO STRENGTH 0F POLYGLYCOLIC ACID OriginalFiled Dec. 23, 1968 '7 Sheets-Sheet '7 52 W4rE/? OUTLET I 3.9 34 46 1' Ti ,1 J0 J I 3a, 1123a 23 39 27 warm I I/VLET /6 I l lil I /5 v 24. /2- vVACUUM SYSTEM ,.-1| J RECORDER VAR/ABLE v RHEOSTAT 3,772,420 7 METHODFOR IMPROVING THE IN-VIVO STRENGTH F POLYGLYCOLIC ACID Arthur Glick,Danbnry, and James B. McPherson, In,

Cos Cob, Conn., assignors to American Cyanamid Company, Stamford, Conn.Original application Dec. 23, 1968, Ser. No. 786,049, now ,Patent No.3,626,948. Divided and this application Sept. 7, 1971, Ser. No. 178,499

Int. Cl. B29c 25/00 U.S. Cl. 264-102 4 Claims ABSTRACT OF THE DISCLOSUREPolyglycolic acid in shaped form (Le. a suture) which is substantiallyfree from vaporizable impurities is provided which has significantlygreater in-vivo strength retention than shaped polyglycolic acidcontaining said vaporizable impurities. The improved polyglycolic acidis prepared by vacuum heating shaped polyglycolic acid containing'vaporizable impurities to vaporize the impurities therefrom, and thenremoving the vaporized impurities from the polyglycolic acid. Anapparatus for conveniently carrying out the above process is alsoprovided.

This is a division of application Ser. 'No. 786,049, filed Dec. 23,1968, now U.S. Pat. 3,626,948.

" BACKGROUND THE INVENTION 1 For many years, virtually all absorbablesutures used in animal and human surgery were prepared from mammalianintestine, such sutures being commonly called catgut sutures.

1 More recently, widespread research efforts have been directed towarddiscovery of a synthetic material which could be readily extruded intofilaments from which sutures could be fabricated which would (1) retaintheir tensile strength after implantation in the body for a sufiicienttime to permit wounds joined together with such sutures to healproperlyand (2) would be absorbed by the body without adverse effectsand within an acceptable time after implantation. Such a material wouldhave many advantages over catgut such as uniformity of composition, and,hopefully, ease of manufacture. These efforts have recently home fruit.U.S. P'at. 3,297,033, for example, describes a synthetic absorbablesuture prepared from polyglycolic acid, said patent herein incorporatedby reference.

Polyglycolic acid can be prepared in a variety of ways. For example, itcan be prepared by heating glycolic acid and then removing water andglycolide from theresulting material after which a catalyst is added tothe residue and the residue heated (U.S. Pat..2,585,427) It can also beprepared as described above except thatthe residue is cooled andcollected as a powder which is then heated at 2.,

an elevated temperature(U.S. Pat. 2,676,945). It can additionallybeprepared bythe polymerization of glycolide which is free from water andacid impurities in the presence of a catalyst (U.S. Pat. 2,668,162).

In order to obtain the strong filaments of polyglyc'olic if polyglycolicacid of sufiiciently high molecular weight scribed above. During thepolymerization, some glycolide monomer fails to polymerize topolyglycolic acid and glycolide contents in the polymer of as much asabout 8% have been observed.

Although entirely acceptable sutures can be prepared from polyglycolicacid containing glycolide, applicants have discovered that:

(1) when glycolide and other impurities which either react with theglycolide or are formed as by-products of a reaction of glycolide with areactive impurity are removed from the polyglycolic acid to the extentpossible by vaporization of the impurities, and

(2) these vaporized impurities are then removed from the environment ofthe suture, that sutures prepared from such substantially impurity-freepolymer exhibit an astonishing enhancement in in-vivo strength retentionas compared to sutures prepared from polymer which contains theseimpurities. In-vivo strength retention is determined by implantingsuture lengths in rabbits and then sacrificing the rabbits at prescribedintervals (usually 7 and/or 15 days after the implantation), whereuponthe suture is removed and the tensile strength of the suture measured inaccordance with standardized procedures.

With the advent of an absorbable polyglycolic acid suture, some attemptshave been made to raise the in-vivo strength retention to previouslyunattainable values while at the same time assuring absorption of thesuture by living tissue within a reasonable time. Ordinarily, it isdesirable that an absorbable suture retain a surgically useful tensilestrength for up to 10 to 15 days after implantation; it is equallyimportant that the suture be absorbed by tissue soon thereafter,preferably within days after implantation. It would, of course, be mostdesirable if a suture could be provided which gave consistently highinvivo tensile strength even after 15 days implantation in tissue whilesimultaneously being substantially absorbed bythe tissue within about 90days after implantation. Achievement of these dual requirements incatgut absorbable sutures can present problems because treatments whichenhance in-vivo strength retention of the suture may extend theabsorption period appreciably. For example, when catgut sutures arechromicized to enhance in vivo strength retention, conditions must bevery carefully controlled to prevent excess chromicizing; otherwise,suture absorption times can be unduly prolonged.

U.S. Pat. No. 3,422,181 issued Jan. 14, 1969 teaches that in-vivo.strength retention can be improved in a polyglycolic acid suture bymerely heating the suture at certain temperatures and atmosphericpressure for a given period of time. However, the improved strength ofthe suture results primarily from an annealing effect within thepolyglycolic acid filaments since, under the conditions described in theapplication, an effective amount of timpurities would not be removedfrom the polymer if they were present therein. Also the application doesnot teach the-importance of removing any volatilized impurities from theenvironment of the suture as will be discussed 'hereinbelow in' greaterdetail. This is not surprisingsince, as mentioned above, little, if any,effective volatilization of impurities occurs under the processconditions of this application.

Patented Nov. 13, 1973 It is an object of this invention, therefore, toprovide a new kind of shaped polyglycolic acid whichis substantiallyfree from vaporizable impurities and which, as a result thereof,exhibits consistently high in-vivo tensile strength even after 15 daysimplantation in living tissue. It is another object to provide shapedpolyglycolic acid having consistently high in-vivo strength retentionafter 15 days while, at the same time, being substantially absorbed byliving tissue within 90 days after implantation. It is also an object ofthis invention to provide a novel process and apparatus which areeminently suitable for preparing the polyglycolic acid of thisinvention.

SUMMARY OF THE INVENTION This invention relates to polyglycolic acid inshaped form which is substantially free from vaporizable impurities.

The term polyglycolic acid or polyglycolic acid in shaped form as usedherein refers to any of the continuous forms into which polyglycolicacid can be fabricated such as by extrusion, molding or such andincludes monofilaments, multifilaments, sheets, film, rod, ribbons, andmolded objects; it also includes polyfilamentary braided strands usefulas absorbable sutures and variously shaped body implants and prostheticdevices such as described in copending application Ser. No. 608,068,filed Jan. 9, 1967, now US. Patent 3,463,158. The invention will bedescribed in terms of a polyglycolic acid multifilamentary braidsuitable for use as an absorbable suture for purposes of clarity;however, the invention is also applicable to various other shaped formsof polyglycolic acid as described above.

A vaporizable impurity is one which can be volatilized from thepolyglycolic acid.

Polyglycolic acid is substantially free from vaporizable impurities whenit exhibits a weight loss of less than 0.4% by weight when it is heatedfor three hours at 135 C. under an absolute pressure of 4 mm. of mercuryin the presence of a cooled surface maintained at a temperature of about25 C., said surface being separated from the polymer by a distance ofabout 2 inches. As the polyglycolic acid is heated, the vaporizableimpurities contained therein are vaporized and diffuse across the gapbetween the polymer and the cooled surface. As the impurities strike thecooled surface they condense to produce a residue on the surface wherebythe impurities are removed from the environment of the polyglycolicacid.

As described heretofore, the removal of these impurities has apronounced effect upon the in-vivo strength retention of a shaped formof polyglycolic acid such as a suture. The impurities removed arebelieved to consist primarily of water, glycolide, and the linear dimerof glycolic acid which is represented by the formula:

I! II OH-CHa-C-O-CHz-G-OH These impurities can arise in the polyglycolicacid in a variety of ways. For example, as described heretofore,glycolide can originate from unpolymerized monomer. If a polyglycolicacid suture containing glycolide is exposed to a moist environment thesuture may pick up water. It is believed that this water reacts readilywith the glycolide to cleave the glycolide ring and form theaforementioned linear dimer of glycolic acid. It is further believedthat the linear dimer of glycolic acid can then react with the highmolecular weight polyglycolic acid in a transesterifi cation reaction toproduce sutures having polyglycolic acid chains of lower molecularWeight which tend, when implanted in living tissue, to give reducedretention of in-vivo tensile strength.

The impurities may also arise if the polymer is subjected to hightemperatures which tend topartially detemperature ofabout 240-250C; andit is possible under these conditions that some polymer can degrade intoglycolide or the linear dimer of glycolic acid. Of course, the glycolidethus formed can react with any moisture present to form additionalundesirable linear dimer. Because of the reactive interrelation betweenwater and glycolide to produce the undesirable linear dimer, it isessential that all three of' these impurities i.e. water, glycolide, andthe linear dimer of glycolic acid be removed. The degree to which thein-vivo strength retention is enhanced is believed to depend upon theextent to which the vaporizable impurities present are removed from thepolymer. Ordinarily, as a greater proportion of these impurities isremoved, a greater enhancement of in-vivo strength retention is noted.

This invention also relates to a process for preparing polyglycolic acidin shaped form which is substantially free from vaporizable impuritieswhich comprises heating shaped polyglycolic acid containing vaporizableimpurities in a dry environment at a temperature of from about 75 C. toabout 160 C. at a sub-atmospheric pressure. 'Under these conditions aneffective amount of vaporizable impurities contained in the polyglycolicacid is removed therefrom. Once these impurities are removed, it isessential to further remove them from the immediate environment of theheated polyglycolic acid. If this is not done, the impurities have astrong tendency, especially when pressures which are not sub-atmosphericare restored, to condense upon the surface of the polymer to product awhite powdery surface coating on the polymer. These impurities also tendto polymerize to harmful higher molecular weight forms and cannot beremoved from the polymer thereby causing an irretrievable loss of thepolymer.

In cases where this deposition of impurities on the surface of thepolyglycolic acid has occurred, the in-vivo as well as packageproperties of the polymer were most unsatisfactory indicating the highlyundesirable effect these impurities can produce. Therefore, means mustbe provided, once these impurities have been vaporized, for removingthem from proximity with the polyglycolic acid. A particularly suitableway for effecting this removal is to provide a cooled surface adjacentto the heated polymer, the cooled surface being maintained at atemperature below that of the heated polymer. After the vaporizedimpurities are removed from the polymer, they diffuse towards thecooling surface and condense thereon whereby they are removed from theenvironment of the polymer.

This invention also relates to an apparatus for removmg and collectingvaporizable impurities from polyglycolic acid in shaped form. In itsmost basic aspects, the shaped polyglycolic acid member is supported inan airtight chamber. Means are provided for applying heat to the memberwithin the chamber. Means are also provided for the creation ofsub-atmospheric pressures within the chamber. The housing containing thechamber is adapted to provide for cooling at least a portion of the wallof said chamber adjacent to the heated member, this portion of thechamber wall being separated from the heated member by a'predetermineddistance. As the member is heated. within the chamber undersub-atmospheric pres ber wall they condense thereon to eflect removal ofthe impurities from the environment of the polyglycolic acid member.

. BRIEF DESCRIPTION OF DRAWINGS FIG. 1 depicts the effect of thetemperature at which a polyfilamentary braid is heated upon variousproperties comparison of the in-vivo properties of polyfilamentarybraids treated inaccord with the process of this invention and braidsnot so treated.

EFIG. depicts the significant upgrading in in-vivo strength retentionwhich can be achieved by the process of this invention lay-comparing thein-vivo properties of poly-filamentary braids which ordinarily havelittle, if any, in-vivo tensile strength after 15 days implantation inliving tissue with the in-vivo properties observed on the same braidsafter treatment in accordance with the process of this invention.

FIGS. 6a and 6b represent an exploded view of an apparatus which issuitable for preparing the shaped polyglycolic acid of this invention.

FIG. 7 is a center sectional view of the assembled apparatus for FIG. 6further including various equipment for controlling process conditionswithin the apparatus.

DESCRIPTION OF THE PREFERRED EMBODIMENTS Polyglycolic acid as typicallyprepared in US. Pat. 2,668,162, or 3,297,033, is conventionally extrudedinto a multifilament which is then divided into various portions for useas sleeves and cores during braiding. A braided polyglycolic acid sutureis prepared from these portions using conventional braiding techniquesand equipment. A portion of the braid thus prepared is weighed and thenwound circumferentially around a hollow metal cylinder. Thecylinder-braid unit is weighed and placed within an Erlenmeyer flaskwith the axis of the cylinder perpendicular to the bottom surface of theflask. The flask is immersed in an oil bath maintained at a temperatureabout 5 C. higher than that at which it is desired to heat the braidlTheupper portion of the flask is not immersed in the oil and is exposed toa room temperature environment. The appropriate sub-atmospheric pressureis then 6 quantity of impurities removed from the braid. The percentweightless of the braid isdeterininedby dividing the quantity ofimpuritiesremoved by-the original'weight of the braid and multiplying by=100fi Thepackage properties, i.e. straight" pull 'and -knot pull, aremeasured on 'both unsterilized braid and braid sterilized by gaseousethylene oxide. There is ordinarily no detectable difierence in packageproperties between sterilized and unsterilized braid. Sterilized braidis then implanted in rabbits for a period of 7 or 15 days, after whichthe braid is removed from the animal and its tensile strength measured,said value being the in-vivo tensile strength. The straight pull isreadily measured using a Scott inclined plane tester (Model Number IP-4)in accord with the method shown in US. Pat. XV, pg. 938. Knot pull issimilarly measured in accord with the procedure shown in US. Pat. XV,pg. 939.

The method described immediately hereinabove was used to gather the datain Tables I to V hereinbelow.

PROCESS CONDITIONS (a) Temperature The eifect of temperature (atconstant pressure and heating time) upon package and in-vivo propertiesand upon the weight loss of sutures treated in accordance with theprocess of this invention is shown by the data of Table I. These dataare graphically presented in FIG. 1. Referring to FIG. 1, it is observedthat no appreciable weight loss occurs until the filament is heated toat least a temperature of C. As soon as appreciable amounts ofimpurities begin to vaporize from the filament, there is a noticeableenhancement in the- 15 day in-vivo straight pull value of the suture.This improvement continues until temperatures in excess of about 160 C.are employed whereupon there is a sharp decrease in in-vivo strength aswell as package straight pull and knot pull. It should be noted thatweight loss of the suture increases at a fairly constant rate astemperature increases until a temperature of about 160 to 180 C. isreached whereupon a sharp and dramatic increase in the amount ofvolatiles released by the suture occurs suggesting that at theseelevated temperatures rapid thermal degradation of the polymer isbeginning to occur. Preferred heating temper atures are from about C. toC. The data of Table I indicate that in-vivo strength retention can beimproved by as much as 222% when the suture is treated within thepreferred temperature range given above.

TABLE I.-THE EFFECT OF TEMPERATURE (4 mm. Hg. for 5 hours) 15-dayln-vivo properties Package properties Straight pull Straight pull Knotpull Di 1Percent: iPercent: Tern erature Percent Dia. a. ncrease ncrease0.? wt. loss (mils) Lb. P.s.l. Lb. P-S-i- (mils) Lb. P.s.i. inlb. inp.s.i

(b) Pressure Data are presentedin Table II which show the efiectofpressure (at constant temperature and heating time) upon package andin-vivo properties. The in-vivo' and weight loss data of Table II arepresented graphically in FIG. 2. is heated has virtually no efiect uponthe package-straight These data indicate that the pressure at which thesuture pull and knot pull; however, pressure does have a pronouncedeffect upon the in-vivo tensile strength of poly- 7 glyeolic,-acid.,Referring to 1316.2, it can be seenthat it is. essent ialllthat thesuture be-heated under conditions-of sub-atmospheric pressure.Merely-heating at atmospheric pressure, .althoughitfdoesremove somevolatiles, has no appreciable effect upon in-vivo strength..; l"his isnot surprising since it wouldnot be expected that glycolide or thelinear dimer of glycolic acid wouldbe removed inany appreciable amountat such pressures. However, as pressureis gradually reduced below oneatmosphere there is 5 curve in FIG. 3).; On ,the-.other-hand,.when'excessively high temperatures i.e. above 160 C., are used, althoughthere is significant removal of volatiles, there is a marlred decreasein the in-vivo strength of the suture as clearly a greater increase inthe amount of impurities removed shown by the dotted 180 C. curve ofFIG. 3. As discussed from the suture with a corresponding increase inthe in-vivo tensile strength of the suture. It is not until pressuresbelow-about 300mm. of mercury are reached that the weight loss andcorresponding enhancement of in-vivo tensile strength becomes readilyapparent although some weight loss and enhancement of tensile strengthdoes occur at pressures in excess of 300 mm. of mercury but less thanone atmosphere. It is, of course, desirable that the pressure bemaintained at as low a value as possible; pressures below about 100 mm.of mercury are preferred and pressures of from .1 to 4 mm. of mercuryare highly preferred.

TABLE II.-EFFEC'I OF PRESSURE (5 hrs. at 135 C.)

above, this is believed to occur at temperatures above 160.? C.'becausethe volatiles which are removed are no longer merely the undesirableimpurities which are removed at temperatures below 160 C. but are thethermal degrada- 15-day in-vivo propertiesstraight pull Percent Peleentincrease increase Lb. p.s.i. in lb. in p.s.i.

(c) Heating time The effect of heating time (at constant pressure andconmultifilament, braided yarn, or such is heated at a temperature ofabout 100 to 150 C. for about 3 hours under stant temperature) is shownby the data of Table III. The 40 an absolute pressure of 1 mm. ofmercury or less.

TABLE IIL-EFFECT OF HEATING TIME (4 mm. Hg and constant temperature)Package properties Straight pull Knot pull 15-day in-vivoproperties-straigl1t pull Percent Percent Percent Templ wt. Die. Die.increase increase Ti (mm) 0.) loss (mils) Lb Psi. Lb. P.s.i. (mils) Lb.P.s.i. in lb. in p.s.i.

c t l 15. 7 14. 8 76, 500 9. 7 50, 100 15. 7 98 5, 100

data of Table III are shown graphically in FIG. 3. Re- Table IV presentsdata which has been gathered on fel'fing G- i can Seen lh Y9 a varietyof difierent sized polyglycolic acidsutures which il e from a suture a1a fixed Peatmg time 7 have been treated in accordance with the processof this i ri a t w the teimpe-raiure at which 51.1mm invention andserves to indicate the astonishing increases is heated with morevolatiles bemg removed as higher in imvivo strength retention (as highas 282% which i used. However re ardless of tern erazi sggi zj zPortion. 6 a fi impurities occur when only small amounts of volatllesare removed 5 moved during the first hourof heating with only minimalfrom the suture. Selected averaged data from Table IV additional removaloccurring as heating continues. are shown graphically in FIG. 4.

- Wtloss Comments Control. (1.57 Treated.

Pere'ent Percent YG Q Q QP-QID 151 17 335.

'(niils) "Lb Pisa;

Suture size 9 1 8 1 7 m zmm mum 12 nn-212n 123 mmmmwmmmmmm mm Aea712001356377 .LLLzLLaa3 20 o2 z. 111111 111111 ,900 Control. ,500 8.45 Treated. ,500 Control. ,600 +105 .54 Treated. 6,600 Control.

+87 .84 Treated.

madam 8834-019 .Rw7 7 6 6 6 -0 7 57793241 0 0 LL0 0 0 1111111 Control..85 Treated.

Referring to FIGS. 6a and 6b, and to FIG. 7, a center sectional view ofthe assembled apparatus, this apparatus comprises metallic base plate 11supported by legs 12. Base plate 11 contains groove 13 which is adaptedto re- Treated: Subjected to 135 C. and Hg for about hours. 'Table Vpresents data whichindicate how polyglycolic acid sutures formerlyhaving little, if any, tensile strength after 15 days implantation inliving tissue were upgraded by treatment in accordance with the processof this invention to sutures not only having acceptable 15 day ceivegasket 14. Base plate 11 contains threaded apertures tensile strengthsbut also having surprisingly high 15 day 15 which are adapted forinsertion of thermocouples up values. For example, in one case, a suturewhich prior through plate 11 into the apparatus (see FIG. 7). Base totreatment by the process of this invention had virtually plate 11 alsocontains threaded aperture 16 adapted for is placed within groove 13. V

Support plate 17 is placed upon base plate 11 and firmly attachedthereto by screws 18 which are threaded into holes 19 in base plate 11.

High resistance wire 20 is wrapped around hollow metallic cylinder 21 toprovide a heating element. Leads "22 of wire 20 pass through apertures23 in the wall of cylinder 21 and into the interior of cylinder 21.Cylinder TABLE V.UPGRADING 0F POLYGLYCOLIC ACID SU'IURE BY APPLICATIONOF.

In-vlvo straight pull after implantatlon in rabbits for- Packageproperties 7 days 15 days Percent Percent Percent change change wt.

in lb. Lb. P.s.l. in 1b.; Lb. P.s.l. loss Comments .89 3,275 0 0Control. -4 8.8 32,270 +880 .74 2,700 1.3-2.5 Treated.

The devolatilized sutures prepared in accordance with I this inventioncan be dyed, coated, needled, sterilized, 5 packaged, and 1.188(1'111accordance with techniques de- DEVOLATILIZA'IION TREATMENT THERETO Die.

(mils) Lb. P.s.l.

no 15 day tensile strength exhibited a tensile strength of 40 connectionto a vacuum system (see FIG. 7). Gasket "14 17,438..p.s.i. aftertreatment by the process by this inven H tion. Selected average datafrom Table V are shown graphically in FIG. 5.. f

scribed for the polyglycolic acid suture disclosed in US."

Pat. 3,297,033.v

Suture size i 21 containing wire ztl is thenins'erted through recess 23hof plat'e .17, the bottom, surface 249i cylinderllcorning to 're'st'dnsurface .25 or base",p1a.te 'lL-Lead WireS'fZZ 7 Apparatus h H FIGS. 6aand 6b represent exploded views of a preferred embodiment of anapparatus which is particularly suitable for removing and collectingvaporiiable'impurities from a polyglycolic acid filament, in accordancewith P at emerge from the apparatus through'apertiir "25a 1, connectingvar new 1 WZF' GsY- I Ave the process of this invention. The explodedview of (the tul'e is a pt a r-.t sh r a e rl g$ l apparatus is bestseen by placing FIG. 6b on top of FIG. and 0111 Of the pp a S h a by all ll k tube. Plate 6a to obtain an overall exploded view of theapparatus. 17 is secured about base 2.7 of cylinder 21 by set screws 28.Spacing collar 29 is then'inserted over the tion 30 of cylinder 21 byset screws 31.

Polyglycolic acid suture braid 32 is circumferentially wrapped aroundhollow metallic cylinder 33. Cylinder 33 is adapted at top portion 34and bottom portion 34a to receive screws 35 which facilitate subsequentremoval means of a wire handle. Cylinder 33 containinglb'raid32 iscarefully slid over collar 29 and cylinder 21 coming. to rest on surface36 of support plate 17. Collar 37 of support plate 17 and collar 29insure that the inner surface of column 33 is uniformly spaced indistance from the outer surface of wires 20 so as to provide uniformheating of braid 32.

Hollow cylinder 38 which is adapted 39 for passage of a liquid coolingmedium through annular space 40 (see FIG. 7) between inner wall 41 andouter wall 42 is then slid over cylinder 33 and braid 32 containedthereon coming to rest on gasket 14 which is mounted in groove 13 ofplate 11. Gasket 43 is placed on the top surface 44 of cylinder 38, andlid 44a is placed on top of gasket 43 to complete assembly of theapparatus.

Referring to FIGS. 6a, 6b, and 7, it will be noted that the apparatuscontains provisions for the insertions of three thermocouples by meansof apertures 15. One thermocouple 45 measures temperature on the outsidesurface 46 of circumferentially wrapped braid 32. A second thermocouple47 measures temperature of the inner surface 48 of cylinder 33. A thirdthermocouple 49 measures the temperature of wire 20. These threethermocouples are connected to temperature recorder 50 for easymonitoring.

The temperature of wire 20 can be adjusted to produce the desiredtemperature at inside wall 48 and the surface 46 of braid 32. Thetemperature of wire '20 required to produce any given temperature atsurface 46 of braid 32 will of course vary depending on the thickness ofair gap 51 between cylinders 27 and 33 as well as on the sufficientlyhigh value to cause the vaporization of any vapotizab'le'.impurities}contained therein. Cooling water -having beenpreviouslyapplied toannular space '40- of the vaporized impurities frombraid 32 gap 54 which separates heated braid 32 -,-from cooled iii? r51'55" i "re 38 t r of the cylinder (while still hot) from the apparatusby 1 er su Ce 0 cy m at con ac mg 1, cooledjsurface 55and'condensing'thereon'whereby their X -a'emoval -frorn the environmentsurrounding'braid 32 is effected;

The thickness of gap 54 can vary considerably provided there is a finitedistance between outer surface 46 'of braid 32 and surface 55 ofcylinder 38. Ordinarily, a gap distance .of up to about 12 inches issuitable with a distance of about 1 to Zinches higher preferred.

If the radial thickness of braid 32 becomes excessive, the temperatureof braid 32 in contact with surface 53 may have to be in excess of 160C. in order to insure a suitably high-temperature at the surface 46 ofbraid 32 20 which is closest to cooled surface 55,thereby creating a arisk of damaging braid closest to hot surface 53 of wall 35 data ofTable VI also'indicate that there is substantially 52. However, whenthicknesses of less than /2 inch are used in the described apparatus,suitable temperatures can be produced throughout the entire radialthickness of 25 braid 32. The acceptable radial braid thickness will, of

course, depend on the particular design of the apparatus. Table VIpresents data gathered using the apparatus described in FIGS. 6d, 6b,and 7. In all cases, there was 30 improvement in the in.-vivo strengthretention of the no difference in package straight pull and knot pullbetween treated and untreated sutures.

L ID UTURES OFENHANCED IN-VIVO STRENGTH RETENTION PRE- TABLE VI XRD VITH THE APPARATUS OF FIGURES 6a, 6!), AND 7 Temperature C.) 01- Packageproperties 15 day in-vivo properties- Outer wall of Inner warll 011dBloating; L0 ti 1 1 Straight pull Knot pull Straight pull B l Outsid baid ra eemen ca one a. (tfg brai cylir ider cylinder sample (mils) Lb.P.s.i. Lb. P.s.l. Lb. P.s.i.

1 See the following- Sample location 1=Braid in contact with the outerwall of the braid cylinder. Sample location 2=Braid midway betweenLocation 1 and the outside wind of the braid.

cylinder.

3 Control.

about to 205 C. and tea temperature 'attheouter surface'53 of wall 52offrom about 100 toabout 160 C.

. After thefapparatus is assembled the appropriate 70 va m sa p ie thm ft re 1: n P e is n plied to wirefl20fsaid'power being adjusted byrheostat 2630' create theaforementioned desir edtemperature at the'yarious' points in the apparatus. 'Afte'r 'a' brief induction' period,the temperature of braid 32 is raised to a 7 Sample location 3=Braidfrom the outside wind of the braid, i.e. the braid farthest removed fromthe outer wall of the braid ..We claim: f 1. A'm'ethod for improving thein-vivo strength retention of .absorbable'polyglycolic acid in shapedform which comprises heating polyglycolic acid in shaped form, whichcontains vaporizable impurities, in a substantally'dry environment at atemperature of from about 100 C. to about C. for a period of time,varying inversely with temperature, of between about 1 hour and 5vhours, at an absolute pressure between about 0.1 mm. and 4-mm.'0fmercury to vaporize therefrom an effective amount of saidimpurities andremoving said vaporized im'puritiesfrom said polyglycolic acid.

' 2. Themethod of claim 1 wherein said impurities are removed from theenvironment of the polyglycolic acid by providing a cooling surfacemaintained at a temperature below about 70 C., said surface separatedfrom said polyglycolic acid by a distance of up to about 12 incheswhereby said vaporized impurities are collected as a residue on saidcooled surface.

3. The method of claim 1 wherein the polyglycolic acid is heated atabout 135 C. and for about 3 hours at an absolute pressure of about 4millimeters of mercury and where the distance between the heatedpolyglycolic acid and the cooling surface is about 2 inches.

4. The method of claim 1 wherein the polyglycolic acid in shaped formcomprises one or more filaments of polyglycolic acid.

10 ROBERT F. WHITE,

References Cited UNITED STATES PATENTS Primary Examiner G. AUVILLE,Assistant Examiner US. Cl. X.R.

UNiren starts rirrn r @PPIICE CERTH EQATE @F QQRREQ'HQN Patent 5J72A2ODated November 15. 1975 Inventor(s) Arthur Glick and James B. McPherson,Jr.

It is certified that error appears in the above-identified patent andthat saidLetters Patent are hereby corrected as shown below:

001. 6 line 73. Delete the following words: "is heated has "Virtually noeffect upon the package straight".

Col; 6 line 74. After the word "suture" insert the following:

--is heated has virtually no effect upon the pack age straight-n Col. 7Table II. Last line in Table II has bee-n omitted. Please insert thefollowing numbers under their respective 1 headings: r

sub-heading ne insert +11}! Col 9 Table IV. Under Package propertiesstraight pull subheading Peslo line 15, delete "86,800" and insert inits place --88,800--..

Under In-vivo straight pull after 15 day implanta tion in rabbitssub-heading Lb. line 20 delete an 1n 1 s place insert -.78--;sub-headingP'osoie line 20 delete "7,600" and in its place insert --7,000--;sub-heading Percent change in- FORM P04 050 (10- 9) USCOMM-DC 60376-PB0W L5. GOVERNMENT PRINTING OFFICE: 19'' O-3II33O UNITED STATES PATENTOFFICE PAGE 2 CERTIFICATE @F QQRRECTIQN Patent No. 5,772,420 DatedNovember 13, 197} Inventor(s) Arthur Glick and James B McPherson Jr.

It is certified that error appears in the above-identified patent andthat said'Letters Patentere herelgy corrected as shown below:.

lb. line delete "+1 9" and insert in its place +T19--; same sub-hea ingline 14 delete "+260" and insert in its place +280 Signed and sealedthis lL th dey of May 1971+,-

A Attest: I

EDWAPJJ I*I.FLETCHE1' ,JR C0v MARSHALL DANN Attesting OfficerCommissioner of Patents

